Charles H. Grisbrook arrived in the Cape Colony from England around 1816. He studied medicine as an apprentice to Dr John Atherstone*, but did not obtain any formal qualifications. By the late 1820's he had developed an active interest in geology and palaeontology. In October 1829 he presented some minerals to the South African Institution, founded in Cape Town earlier that year as the only scientific society in the Cape Colony. The next year he published a brief paper, "Notes on South African geology" in the South African Quarterly Journal (1830, Vol. 1(4), pp. 446-447), following an earlier article on South African geology in the same journal by Reverend George Thom*. Grisbrook drew attention to the fossiliferous deposits near Uitenhage, where he and W.L. von Buchenroder* had collected fine specimens on the banks of the Swartkops River in 1828, while shell and plant fossils had been collected on the banks of the Sondagsrivier by Dr. W. Gill*. He also mentioned the approximate locations where various interesting minerals and rock types could be found.
Meanwhile, in 1827, he had seen a large fossil tooth in the home of Mr Baird, a former magistrate of Beaufort West, which had been found by a young De Klerk. Grisbrook and Baird visited the site where it had been discovered, in an amphitheatre formed by the Nuweveld range near Beaufort West, where they found the remains of two large skeletons. The tooth represents the earliest known fossil of a vertebrate animal found in South Africa. In October 1831 Grisbrook, then a corresponding member of the South African Institution, published an account of the finds, "Organic remains in the Karroo", in the South African Quarterly Journal (Vol. 1(5), pp. 25-27).
Grisbrook was licensed to practice as an apothecary in 1832. He settled in Graaff-Reinet, from where he complained to the Colonial Medical Committee in 1844 that medical practitioners were practising also as apothecaries, to his disadvantage, and suggested a revision of the laws pertaining to the vending of medicines. Two years later he published A letter to the Right Honourable Secretary of State for the Colonies on the pending Kaffir question, with an appendix including the various memorials and petitions by the colonists at the Cape to the Cape and British governments during 1835-1837. From 1855 to 1857 he represented Graaff-Reinet as a member of the Legislative Assembly. On 1 September 1833 he married Maria T. Bam in Swellendam. He subsequently married Johanna E.M. Liesching in Graaff Reinet in 1841. His daughter Charlotte Isabella later married Francis Guthrie*. The type specimen of the heath Erica grisbrookii, named by Guthrie and H. Bolus*, was collected either by Charles H. Grisbrook or (more probably) by his son Charles F.S. Grisbrook. The elder Charles requested permission to act as a chemist in 1862 and was still listed as an apothecary in 1865.